Factors and agents which are capable of influencing the formation, hydrolysis and activity of cyclic AMP will be examined. These include hormones and agents which influence its rate of synthesis by adenylate cyclase, hydrolysis by cyclic nucleotide phosphodiesterase and other possible pathways for metabolism. In addition, the release of cyclic AMP from tissues will be examined. A material which appears to be a 3',5'-cyclic nucleotide monophosphate and a possible metabolite of cyclic AMP will be characterized and identified. The mechanism whereby this unknown nucleotide inhibits cyclic AMP activation of protein kinase will be examined. Effects of other cyclic AMP analogues will also be evaluated. Also the effects of the accumulation of cyclic GMP in tissues on cyclic AMP synthesis, hydrolysis and activity will be studied. Concentrations of cyclic AMP and cyclic GMP in body fluids (urine, plasma, and spinal fluid) will be examined in normal subjects and patients with various endocrine and metabolic diseases. In addition, the effects of various hormones and cyclic nucleotide phosphodiesterase inhibitors on cyclic nucleotide levels in extracellular fluids will be studied. These observations will be evaluated for their applicability and usefulness in diagnosing several diseases and examining their pathophysiology.